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HPRT Deficiency

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acorrigan's version from 2017-05-11 20:51

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Question Answer
What chromosome is the HPRT gene located on?X
What is the inheritance pattern for this disorder?X-linked, hemizygous males are affected, carrier females aren't usually
What is the best test to detect female carriers and why?Molecular characterisation of the mutation. They are rarely picked up on enzyme assay, not quite known why but possibly due to preferential survival & maturation of cells with active X chromosome with WT allele. because
Are female carriers affected?They have over-production of uric acid throughout their lives; however, at menopause serum uric acid levels increase resulting in gout.
What are the key signs of HPRT full or partial deficiency in laboratory tests?High plasma uric acid, absent or reduced HPRT enzyme activity as measured in red cell lysates.
How can overproduction of uric acid be detected in infants?Uric acid crystals in the nappy
What are the clinical manifestations of HPRT deficiency?Hyperuricaemia leads to gout, uric acid excreted in the urine can appear as crystals, stones in kidneys, urethra and bladder, affected males have dev delay, particularly hypotonia leading to delayed sitting and some with severe deficiency never walk. Motor deficiencies which mirror cerebal palsy. Intellectual disability varies in accordance with the level of enzyme activity and there is often a lack of speech, LNS cases have self injurous behaviour.
What is the normal function of HPRT?It is involved in the purine salvage pathway, recycling guanine and hypoxanthine to GMP and IMP.
How is partial HPRT deficiency known?Kelley Seegmiller
What type of mutations are associated with full and partial deficiency respectively?Frameshift - resulting from indels, nonsense = LNS. Missense mutations have been reported to be associated with both partial and complete deficiency depending on consequence and location ie, active site.
Where is HPRT expression highest & why is this important?Brain, de novo purine synthesis is lower in the brain so can't compensate for the defect in purine recycling
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